Field of the Invention
This invention is concerned with new organic compounds and more specifically with dimethylaminoalkyl-3',4'-dihaloanilides III, pharmacologically acceptable acid addition salts, the use of compounds of formula III and its salts and a synthesis therefor.
The novel compounds III and the processes of production thereof can be illustratively represented as follows: ##STR3## wherein A.sub.o is selected from the group consisting of --(CH.sub.2).sub.2 --; --(CH.sub.2).sub.3 --; ##STR4## wherein A.sub.o ' is --(CH.sub.2).sub.4 or --(CH.sub.2).sub.5 --; wherein X is bromo or chloro; wherein X' is chloro, bromo or iodo and wherein R is ethyl, cyclopropyl or vinyl.
The more preferred end products of this synthesis are of the formula IIIA: ##STR5## where A is selected from the group consisting of --(CH.sub.2).sub.2 --; --(CH.sub.2).sub.3 --; --(CH.sub.2).sub.4 -- and --(CH.sub.2).sub.5 --; ##STR6## and wherein X is bromo or chloro.
The most preferred compounds of this invention are of the formula IIIB: ##STR7## wherein A' is ethylene or trimethylene.
Compounds of similar structures are shown in U.S. Pat. No. 3,016,281; however, these patented compounds are analgesics. The present compounds on the other hand are anti-depressive.
U.S. Pat. No. 3,573,320 discloses but does not claim anti-depressant agents of the formula: ##STR8## wherein B is oxygen or sulfur; R.sub.2 is ##STR9## in which n is 2 or 3; R.sub.4 is H or alkyl, or ##STR10## is morpholino, piperidino, pyrrolidino or piperazino; R.sub.3 is alkyl, aryl, etc.
U.S. Pat. No. 3,234,276 and French Pat. No. 2,073,286 (Chem. Abstracts 77,88108) also claim related products, but for different uses.
However, none of the references above reads on the new anti-depressant agents of this invention.
The process I of this invention comprises: heating a mole equivalent of 3,4-dihaloaniline I with about 1/2 to 1 mole equivalent of a dimethylaminoalkyl halide to give compound II, (the excess of compound I provides the base to accept the hydrogen halide moiety generated in this reaction) and acylating compound II, e.g., with the chlorides or bromides of propionic acid, acrylic acid or cyclopropanecarboxylic acid in the presence of a base, or with propionic anhydride to obtain the corresponding compound of Formula IV.
The process II of this invention comprises: heating a mole equivalent of 3,4-dihaloaniline with about 1 mole equivalent of N,N-dimethylamino halobutyramide or -valeramide to give compound V; reducing V with metal hydride to give compound VI; and acylating compound VI to give compound VII.
Such metal hydrides include: lithium aluminum hydride, sodium cyanoborohydride, borane, diborane.
The invention also encompasses the pharmacologically acceptable acid addition salts of the compounds of formula III (including the preferred compounds of formulae IIIA and IIIB). These salts comprise the hydrochlorides, hydrobromides, sulfates, malates, maleates, tartrates, lactates, citrates, cyclohexanesulfamates, methanesulfonates and the like which are prepared by reacting compounds of Formula III with a stoichiometrically calculated amount of the selected acid, in aqueous or ethereal solution, and finally evaporating the solvent.
The invention also comprises the use of the compounds of Formula III or the salts thereof, described above, in pharmaceutical formulations for treating depressions of endogenous and/or exogenous character.